Pyrene Based Schiff Base for Cascade Fluorescent "On-Off" Detection of Aluminium(III) and Fluoride ions and its Applications in Live Cells Imaging.

An easy-to-prepare pyrene-based Schiff base PNZ was synthesized by condensing equimolar amount of 1-pyrenebutyric hydrazide with 2-hydroxy-naphthaldehyde, and employed as a fluorescent chemosensor for in-situ cascade detection of aluminium (Al3+) and fluoride (F-) ions. In DMSO:H2O (1:1, v/v), the weakly emissive PNZ showed a significant fluorescence enhancement at 455 nm selectively upon the addition of Al3+ due to the complexation-induced formation of a pyrene excimer. Schiff base PNZ and Al3+ formed a complex in 2:1 binding ratio with the estimated binding constants of K1:1 = 9826.01 M-1 and K2:1 = 3188.49 M-1. The sensing mechanism was explored by performing quantum mechanical calculations and 1H NMR titration of PNZ with Al3+. The in-situ formed PNZ-Al3+ complex species enabled the fluorescent turn-off detection of F-. Using PNZ and PNZ-Al3+, the concentrations of Al3+ and F- ions can be detected down to 2.89×10-7 M and 1.88×10-7 M, respectively. The cytotoxicity of the PNZ and its ability to bioimage Al3+ and F- ions was examined in the human cervical cancer cell line. Finally, the receptor PNZ was applied for the quantification of Al3+ and F- ions in various real samples, such as tap water, river water, rainwater, mouthwash, and toothpaste.

Inhibition of Benzo[a]pyrene-induced DNA Adduct in Buccal Cells of Smokers by Black Raspberry Lozenges.

Using LC-MS/MS analysis we previously showed for the first time (Carcinogenesis 43:746-753, 2022) that levels of DNA damage-induced by benzo[a]pyrene (B[a]P), an oral carcinogen and tobacco smoke (TS) constituent, were significantly higher in buccal cells of smokers than those in non-smokers; these results suggest the potential contribution of B[a]P in the development of oral squamous cell carcinoma (OSCC) in humans. Treating cancers, including OSCC at late stages even with improved targeted therapies, continues to be a major challenge. Thus interception/prevention remains a preferable approach for OSCC management and control. In previous preclinical studies we and others demonstrated the protective effects of black raspberry (BRB) against carcinogen-induced DNA damage and OSCC. Thus, to translate preclinical findings we tested the hypothesis, in a Phase 0 clinical study, that BRB administration reduces DNA damage induced by B[a]P in buccal cells of smokers. After enrolling 27 smokers, baseline buccal cells were collected before the administration of BRB lozenges (5/day for 8 weeks, 1 gm BRB powder/lozenge) at baseline, at the middle and the end of BRB administration. The last samples were collected at four weeks after BRB cessation (washout period). B[a]P-induced DNA damage (BPDE-N2-dG) was evaluated by LC-MS/MS. BRB administration resulted in a significant reduction in DNA damage: 26.3% at the midpoint (p = 0.01506) compared to baseline, 36.1% at the end of BRB administration (p = 0.00355), and 16.6% after BRB cessation (p = 0.007586). Our results suggest the potential benefits of BRB as a chemopreventive agent against the development of TS-initiated OSCC.

Oral toxicity assessment and the mitigation of lung carcinogenesis by phytol and α-bisabolol combination treatment in swiss albino mice: insights into redox enzyme modulation and caspase-dependent cell death mechanisms.

This study examined the safety and potential anti-lung cancer effects of combinations of phytol and α-bisabolol in Swiss albino mice. Both acute and subacute toxicity assessments showed that the combination of phytol and α-bisabolol is safe, with no adverse effects observed at higher concentrations. Hematological, biochemical, and histopathological tests showed no signs of toxicity in the heart, lungs, liver, spleen, and kidneys. The LD50 was greater than 2000 mg/kg, indicating a large safety margin. Histopathological analysis confirmed cancer induction in the B(a)P-induced group, which had significantly altered relative lung weights. Lung weight increased slightly pre and post-treatment, but histopathology showed normal alveolar epithelium. GSH and SOD levels increased significantly in B(a)P-exposed groups, indicating an adaptive antioxidant response. CAT levels increased significantly in the post-treatment group, demonstrating the role of combination of phytol and α-bisabolol in protecting against B(a)P-induced oxidative damage. Upregulation of Bax and downregulation of Bcl-2 caused a pro-apoptotic environment, suggesting a way to inhibit malignant cell survival. Modulation of caspase-3 and caspase-9 showed the complexity of carcinogen-induced apoptotic signaling. In conclusion, phytol and α-bisabolol were found to be safe and organ-protective, and demonstrated no acute or subacute toxicity. They modulate antioxidant defenses and apoptotic pathways, which may help prevent and treat lung cancer.

Bifunctional photocatalyst/hydrogel composites: Synergistic effects and degradation mechanisms for the degradation of benzo(a)pyrene in smoked sausages.

Benzo(a)pyrene (B(a)P) is a structurally stable and carcinogenic compound, and B(a)P deposition and transport from smoking environment particulates to smoked meat products is a global challenge. In this study, a novel photosensitive bifunctional composite gel (ST/SiO2-Mn) was successfully synthesized as a reliable material for reducing PM2.5-B(a)P in the smoke environment. B(a)P removal experiments demonstrated that the adsorption and filtration properties of the gel effectively reduced the emission of PM2.5-B(a)P in smoke environment. The ST/SiO2-Mn gel removed 88.5 % of PM2.5-B(a)P in 240 min, which further led to a 59.7 % decrease in B(a)P on the sausage surface. In addition, photocatalytic experiments demonstrated that the ST/SiO2-Mn composite could effectively remove B(a)P, and 50 µg/mL B(a)P could be completely degraded within 20 min. Free radical trapping experiments showed that superoxide radicals (•O2-) contributed significantly to the degradation process. In conclusion, this study provides valuable insights for effective PM2.5-B(a)P degradation without increasing economic burden.

Role of calcium salts in modulating benzo[a]pyrene levels in barbecued pork sausages: A study on quality attributes and safety.

Benzo[a]pyrene (BaP), known for its carcinogenic and mutagenic properties, is a marker of polycyclic aromatic hydrocarbons (PAHs). This study aimed to investigate the effect of partially replacing sodium chloride with different calcium salts (calcium chloride, calcium gluconate, calcium citrate, and calcium lactate) on BaP formation in barbecued pork sausages. The results revealed that all four calcium salts inhibited BaP formation in barbecued pork sausages (P < 0.05). Specifically, calcium gluconate showed the most significant effect on BaP inhibition, with an inhibition rate of 61.82 %. Furthermore, calcium salts were found to inhibit lipid oxidation in barbecued pork sausages while promoting the Maillard reaction. Further validation experiments used resveratrol and sodium sulfite as lipid oxidation and Maillard reaction inhibitors, respectively. These results indicated that lipid oxidation is the primary pathway for BaP production in barbecued pork sausage and that the addition of calcium salts can effectively block this process.

Benzo[a]pyrene exposure induces anxiety-like behaviors in the mice through brain metabolic alterations.

The deleterious health impacts of polycyclic aromatic hydrocarbons (PAHs) on the population have been extensively substantiated and acknowledged. Mounting evidence underscores that PAH exposure is closely linked to an elevated risk of mental disorders, particularly in populations experiencing occupational and high-level exposure. In this study, we aimed to investigate the mechanisms underlying anxiety-like behaviors induced by different dosages of PAHs, with a concentrated focus on brain region-specific metabolic alterations in mice using various metabolomics approaches. Male C57BL/6 mice were exposed to benzo[a]pyrene (B[a]P), a typical PAH, through gavage at occupational exposure and EPA toxicologically relevant dosages (2.0 and 20.0 mg/kg/day) for 21 days, respectively. Behavioral assessments revealed that occupational exposure to B[a]P induced anxiety-like behaviors in C57BL/6 mice. Meanwhile, elevated serum norepinephrine and corticotropin-releasing hormone further confirmed the anxiety-inducing effects of B[a]P exposure. Metabolomics analysis uncovered dysregulation across various metabolic pathways following B[a]P exposure, encompassing brain neurotransmitter, organic acid, amino acid, lipid, fatty acid, and cholesterol. Anxiety levels and lipid metabolic abnormalities were notably exacerbated at the higher dosage, despite being only a 10-fold increase. Of particular significance, a decrease in lysophosphatidic acid (LPA) and lysophosphatidylserine (LPS) emerged as pivotal indicators of B[a]P neurotoxicity. Spatial-resolved metabolomics further demonstrated distinctive lipid and metabolite profiles across different brain subregions after exposure to B[a]P. Remarkably, alterations were specifically observed in the anxiety-related brain regions, such as the hippocampus, cortex, white matter, and thalamus, varying with exposure dosages. These findings underscore the significance of brain metabolic abnormalities in the development of mental disorders triggered by B[a]P exposure and highlight the need for establishing precise exposure limits of B[a]P to safeguard public mental health.

Exploration of microRNAs from blood extracellular vesicles as biomarkers of exposure to polycyclic aromatic hydrocarbons.

Exposure to polycyclic aromatic hydrocarbons (PAHs), ubiquitously environmental contaminant, leads to the development of major toxic effects on human health, such as carcinogenic and immunosuppressive alterations reported for the most studied PAH, i.e., benzo(a)pyrene (B(a)P). In order to assess the risk associated with this exposure, it is necessary to have predictive biomarkers. Thus, extracellular vesicles (EVs) and their microRNA (miRNA) contents, have recently been proposed as potentially interesting biomarkers in Toxicology. Our study here explores the use of vesicles secreted and found in blood fluids, and their miRNAs, as biomarkers of exposure to B(a)P alone and within a realistic occupational mixture. We isolated EVs from primary human cultured blood mononuclear cells (PBMCs) and rat plasma after PAH exposure and reported an increased EV production by B(a)P, used either alone or in the mixture, in vitro and in vivo. We then investigated the association of this EV release with the blood concentration of the 7,8,9,10-hydroxy (tetrol)-B(a)P reactive metabolite, in rats. By performing RNA-sequencing (RNA-seq) of miRNAs in PBMC-derived EVs, we analyzed miRNA profiles and demonstrated the regulation of the expression of miR-342-3p upon B(a)P exposure. We then validated B(a)P-induced changes of miR-342-3p expression in vivo in rat plasma-derived EVs. Overall, our study highlights the feasibility of using EVs and their miRNA contents, as biomarkers of PAH exposure and discusses their potential in environmental Toxicology.

Transcriptomic analysis-based study on the response mechanism of juvenile golden cuttlefish (Sepia esculenta) to benzo[a]pyrene exposure.

Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon from incomplete combustion, builds up in coastal regions through river runoff, atmospheric deposition, and coastal activities. BaP's lipophilicity and stability lead to persistent environmental impacts due to its resistance to degradation. The economically valuable golden cuttlefish, Sepia esculenta, often spawns and hatches in shallow waters, making it prone to BaP exposure. This study employs transcriptomic analysis to initially investigate juvenile golden cuttlefish's response to BaP. The results indicate that BaP exposure significantly affects various physiological and molecular functions of the juveniles, particularly affecting pathways related to immune and inflammatory responses, metabolic regulation, and nervous system functions. Functional enrichment and PPI network analyses identified key genes such as HSGALT-like, ASAH1-like, and GTL-like in the BaP response. These genes exhibited a suppressive trend during short-term exposure, indicating that BaP exposure may influence lipid metabolism, energy conversion, and digestive functions at the genetic level, which could further disrupt the overall physiological state and developmental processes of juvenile golden cuttlefish. The study offers novel insights into BaP's effects on juvenile golden cuttlefish and marine life, aiding marine ecosystem and biodiversity conservation.

Black alder's (Alnus glutinosa L.) defense against polycyclic aromatic hydrocarbons (PAHs).

Polycyclic aromatic hydrocarbons (PAHs) are one of the most common groups of pollutants that have toxic and carcinogenic effects. Black alder trees (Alnus glutinosa L.) have been used to remediate contaminated soils from industrial pollutants and heavy metals; however, their usefulness for PAH remediation is unclear. In this study, we examined the response of seedlings from four alder half-sib families (genetic groups sharing the same mother but different fathers) to exposure to four PAHs-phenanthrene, pyrene, naphthalene, and fluoranthene-each at three concentrations. Plant growth parameters were evaluated, and concentration of secondary metabolites and antioxidant activity were measured. The results of the morphological parameters showed that in general, higher PAH concentrations had a more negative effect on tree vitality than lower concentrations (shoot growth reduction by up to 76%). Each half-sib family also exhibited distinct responses in total phenol content (TPC) when exposed to varying concentrations of pollutants, with reductions in TPC ranging from 4 to 52% across different genetic lineages. Enzyme activity also varied between families, pollutants, and their concentrations; for example, while phenanthrene generally increased glutathione S-transferase (GST) activity in the 13-99-1K and 38-61-7K half-sib families, it unexpectedly decreased GST levels by 23% and 29% in the seedlings of the 26-133-6K and 41-65-7K families, respectively, emphasizing the nuanced and divergent enzymatic responses observed in this study. Further secondary metabolite and antioxidant activity analysis revealed distinct variations in the way PAHs impact the defense mechanism of alder seedlings from different genetic groups-prioritizing either enzymatic or non-enzymatic systems. To sum up, analyzing the varying effects of PAHs on distinct half-sib families of alders can prove advantageous in identifying the most efficient black alder genetic families for phytoremediation purposes.

Molecular Design and DFT Analysis of High-performance Dyes Based on Pyrene with Different Donor Parts and Their Optoelectronic Applications.

The performance and efficacy of dyes, which are crucial photon-harvesting components in dye-sensitized solar cells (DSSCs), must be meticulously analysed at the molecular level. This research focuses on a theoretical investigation of dye characteristics rather than the synthesis of novel compounds. Using Density Functional Theory (DFT) and Time-Dependent DFT (TD-DFT), we have analysed six D-π-A structure dyes designed with pyrene as the π-bridge and various functional groups as donors. Our study examines their geometrical, electronic, optical, electronic localization, and electrochemical properties. The findings reveal that these theoretically designed D-π-A dyes show significant improvements in light-harvesting efficiency, open-circuit photovoltage, electron injection efficiency, and overall photovoltaic performance. The analysis indicates effective electron injection from each dye into the conduction band of TiO2, followed by efficient regeneration and enhanced intra- and intermolecular charge transfer properties. The incorporation of pyrene as a π-bridge and the use of different functional groups as donors are crucial for facilitating electron transfer from the donor to the acceptor region. Among the dyes studied, the D-π-D modified dye demonstrates superior theoretical performance, attributed to its higher energy levels of the lowest unoccupied molecular orbital and greater oscillator strengths for excited states. This results in improved intramolecular electron transfer and electron injection into the conduction band of TiO2, followed by effective regeneration. Overall, our study highlights the potential of these theoretically modeled dyes as highly promising sensitizers for DSSCs, due to their exceptional optical and electronic properties and impressive photovoltaic parameters. These findings position these molecular structures as strong candidates for future applications in organic DSSCs.

Synergistic Toxicity of Pollutant and Ultraviolet Exposure from a Mitochondrial Perspective.

Ultraviolet (UV) exposure and atmospheric pollution are both independently implicated in skin diseases such as cancer and premature aging. UVA wavelengths, which penetrate in the deep layers of the skin dermis, exert their toxicity mainly through chromophore photosensitization reactions. Benzo[a]pyrene (BaP), the most abundant polycyclic aromatic hydrocarbon originating from the incomplete combustion of organic matter, could act as a chromophore and absorb UVA. We and other groups have previously shown that BaP and UVA synergize their toxicity in skin cells, which leads to important oxidation. Even if mitochondria alterations have been related to premature skin aging and other skin disorders, no studies have focused on the synergy between UV exposure and pollution on mitochondria. Our study aims to investigate the combined effect of UVA and BaP specifically on mitochondria in order to assess the effect on mitochondrial membranes and the consequences on mitochondrial activity. We show that BaP has a strong affinity for mitochondria and that this affinity leads to an important induction of lipid peroxidation and membrane disruption when exposed to UVA. Co-exposure to UVA and BaP synergizes their toxicity to negatively impact mitochondrial membrane potential, mitochondrial metabolism and the mitochondrial network. Altogether, our results highlight the implication of mitochondria in the synergistic toxicity of pollution and UV exposure and the potential of this toxicity on skin integrity.

Benzo(a)pyrene exposure during pregnancy leads to germ cell apoptosis in male mice offspring via affecting histone modifications and oxidative stress levels.

Infertility has gradually become a global health concern, and evidence suggests that exposure to environmental endocrine-disrupting chemicals (EDCs) represent one of the key causes of infertility. Benzo(a)pyrene (BaP) is a typical EDC that is widespread in the environment. Previous studies have detected BaP in human urine, semen, cervical mucus, oocytes and follicular fluid, resulting in reduced fertility and irreversible reproductive damage. However, the mechanisms underlying the effects of gestational BaP exposure on offspring fertility in male mice have not been fully explored. In this study, pregnant mice were administered BaP at doses of 0, 5, 10 and 20 mg/kg/day via gavage from Days 7.5 to 12.5 of gestation. The results revealed that BaP exposure during pregnancy disrupted the structural integrity of testicular tissue, causing a disorganized arrangement of spermatogenic cells, compromised sperm quality, elevated levels of histone modifications and increased apoptosis in the testicular tissue of F1 male mice. Furthermore, oxidative stress was also increased in the testicular tissue of F1 male mice. BaP activated the AhR/ERα signaling pathway, affected H3K4me3 expression and induced apoptosis in testicular tissue. AhR and Cyp1a1 were overexpressed, and the expression of key molecules in the antioxidant pathway, including Keap1 and Nrf2, was reduced. The combined effects of these molecules led to apoptosis in testicular tissues, damaging and compromising sperm quality. This impairment in testicular cells further contributed to compromised testicular tissues, ultimately impacting the reproductive health of F1 male mice.

Complex Formation of Ag+ and Li+ with Host Molecules Modeled on Intercalation of Graphite.

Pi-stacked and box-shaped host molecules with xanthene as the basis and pyrene as the π-plane were synthesized to verify cation-π interactions between graphene and metal cations. Since crystal structure analysis was not available, DFT calculations were performed to determine the optimized structure, and the π-planes were found to have a slipped parallel structure, with average distances of 456.2-581.0 pm for the stacked compound and 463.4-471.4 pm for the box-shaped compound. Li+ and Ag+ were chosen as acceptors for complexation with metal ions, and their interactions with the π-plane were clarified by NMR titration. Clearly, the interaction with metal ions increased when pyrene π-planes were stacked rather than the pyrene itself. In the stacked compound, the association constants of Ag+ and Li+ were similar; however, in the box-shaped host molecule, only Ag+ had moderate coordination ability, but the interaction with Li+ was very weak, comparable to the interaction with pyrene. As a result, intercalation is more likely to occur in stacked host compound 1, which has some degree of freedom in the pyrene rings, than in the box-shaped compound.

Potential impact of the 2023 Lahaina wildfire on the marine environment: Modeling the transport of ash-laden benzo[a]pyrene and pentachlorophenol.

The Lahaina urban/wildland fire event is considered the deadliest wildfire in the past century of U.S. history. This fire resulted in over 2200 building structures destroyed or damaged, approximately 4000 automobiles were incinerated and between 450 and 878 ha of grassland burned in areas adjoining the town of Lahaina, Maui County, State of Hawaii, U.S.A. One of the most abundant contaminants of both wildland and urban fires is the incomplete combustion product, benzo[a]pyrene. Pentachlorophenol from burned and unburned utility poles/residential burn sites enter into navigable waters, thus posing a serious risk to the water quality of coastal waters. The Risk Quotient Plumes for benzo[a]pyrene and pentachlorophenol, mobilized from Lahaina into coastal waters were calculated based on a hydrodynamic analysis and an integrated ecological risk assessment. This plume was simulated using rainfall events in November 2022 as a proxy for the first major rainfall event expected in Lahaina in 2024. The models indicated that the estimated levels of benzo[a]pyrene and pentachlorophenol posed a risk to near shore habitants within 2 km of Lahaina. The levels of pentachlorophenol were more widespread than benzo[a]pyrene and were predicted to pose a hazard to marine life as far away as Molokini Shoal Marine Life Conservation District and 'Ahihi-Kina'u Natural Area Reserve. Fisheries species captured near these areas should be tested for consumption safety.

Remediation of benzo[α]pyrene contaminated soil using iron naturally bearing in tropical soil: A new frontier in catalyst-free in soil remediation.

Nature iron is considered one of the promising catalysts in advanced oxidation processes (AOPs) that are utilized for soil remediation from polycyclic aromatic hydrocarbons (PAHs). However, the existence of anions, cations, and organic matter in soils considered impurities that restricted the utilization of iron that was harnessed naturally in the soil matrix and reduced the catalytic performance. In this regard, tropical soil naturally containing iron and relatively poor with impurities was artificially contaminated with 100 mg/50 g benzo[α]pyrene (B[α]P) and remediated using a slurry phase reactor supported with persulfate (PS). The results indicated that tropical soil containing iron and relatively poor with impurities capable of activating the oxidants and formation of radicals which successfully degraded B[α]P. The optimum removal result was 86% and obtained under the following conditions airflow = 260 mL/min, temperature 55 °C, pH 7, and [PS]0 = 1.0 g/L, at the same experimental conditions soil organic matter (SOM) mineralization was 48%. After the remediation process, there was a significant reduction in iron and aluminum contents, which considered the drawbacks of this system. Experiments to scavenge reactive species highlighted O2•- and SO4•- as the main radicals that oxidized B[α]P. Additionally, monitoring of by-products post-remediation aimed to assess toxicity and elucidate degradation pathways. Mutagenicity tests yielded positive results for two B[α]P by-products. The toxicity tests considered were the lethal concentration of 50% (LC50 96 h) for fat-head minnows revealed that all B[α]P by-products were less toxic than the parent pollutant itself. This research marks a significant advancement in soil remediation by advancing the use of the AOP method, removing the requirement for additional catalysts in the AOP system for the removal of B[α]P from soil.

Benzo[a]pyrene exposure prevents high fat diet-induced obesity in the 4T1 model of mammary carcinoma.

Tumor metastasis is the main cause of death in triple-negative breast cancer (TNBC) patients. TNBC is the most aggressive subtype of breast cancer lacking the expression of estrogen, progesterone, and human epidermal growth factor 2 receptors, thereby rendering it insensitive to targeted therapies. It has been well-established that excess adiposity contributes to the progression of TNBC; however, due to the aggressive nature of this breast cancer subtype, it is imperative to determine how multiple factors can contribute to progression. Therefore, we aimed to investigate if exposure to an environmental carcinogen could impact a pre-existing obesity-promoted cancer. We utilized a spontaneous lung metastatic mouse model where 4T1 breast tumor cells are injected into the mammary gland of BALB/c mice. Feeding a high fat diet (HFD) in this model has been shown to promote tumor growth and metastasis. Herein, we tested the effects of both a HFD and benzo(a)pyrene (B[a]P) exposure. Our results indicate that diet and B[a]P had no tumor promotional interaction. However, unexpectedly, our findings reveal an inhibitory effect of B[a]P on body weight, adipose tissue deposition, and tumor volume at time of sacrifice specifically under HFD conditions.

Recent trends and future perspectives of photoresponsive-based mercury (II) sensors and their biomaterial applications.

Recent advancements in the field of photoresponsive-based mercury (II) sensors have witnessed a surge in research focused on enhancing detection capabilities. Leveraging innovations in materials science, particularly with quantum dots, nanomaterials, and organic semiconductors, these sensors exhibit improved selectivity and sensitivity. Beyond traditional applications, such as environmental monitoring, the integration of photoresponsive principles with emerging technologies like the internet of things (IoT) and wearable promises real-time and remote mercury (II) ion detection. The on-going efforts also explore multifunctional sensors and miniaturization for on-site applications, addressing current challenges and paving the way for broader commercialization. This dynamic landscape underscores the potential for these sensors to play a crucial role in ensuring the effective monitoring and management of mercury (II) levels in diverse settings.

Trajectories of long-term exposure to PCB153 and Benzo[a]pyrene (BaP) air pollution and risk of breast cancer.

BACKGROUND: While genetic, hormonal, and lifestyle factors partially elucidate the incidence of breast cancer, emerging research has underscored the potential contribution of air pollution. Polychlorinated biphenyls (PCBs) and benzo[a]pyrene (BaP) are of particular concern due to endocrine-disrupting properties and their carcinogenetic effect. OBJECTIVE: To identify distinct long term trajectories of exposure to PCB153 and BaP, and estimate their associations with breast cancer risk. METHODS: We used data from the XENAIR case-control study, nested within the ongoing prospective French E3N cohort which enrolled 98,995 women aged 40-65 years in 1990-1991. Cases were incident cases of primary invasive breast cancer diagnosed from cohort entry to 2011. Controls were randomly selected by incidence density sampling, and individually matched to cases on delay since cohort entry, and date, age, department of residence, and menopausal status at cohort entry. Annual mean outdoor PCB153 and BaP concentrations at residential addresses from 1990 to 2011 were estimated using the CHIMERE chemistry-transport model. Latent class mixed models were used to identify profiles of exposure trajectories from cohort entry to the index date, and conditional logistic regression to estimate their association with the odds of breast cancer. RESULTS: 5058 cases and 5059 controls contributed to the analysis. Five profiles of trajectories of PCB153 exposure were identified. The class with the highest PCB153 concentrations had a 69% increased odds of breast cancer compared to the class with the lowest concentrations (95% CI 1.08, 2.64), after adjustment for education and matching factors. The association between identified BaP trajectories and breast cancer was weaker and suffered from large CI. CONCLUSIONS: Our results support an association between long term exposure to PCB153 and the risk of breast cancer, and encourage further studies to account for lifetime exposure to persistent organic pollutants.

High Expression of AhR and Environmental Pollution as AhR-Linked Ligands Impact on Oncogenic Signaling Pathways in Western Patients with Gastric Cancer-A Pilot Study.

The vast majority of gastric cancer (GC) cases are adenocarcinomas including intestinal and diffuse GC. The incidence of diffuse GC, often associated with poor overall survival, has constantly increased in Western countries. Epidemiological studies have reported increased mortality from GC after occupational exposure to pro-carcinogens that are metabolically activated by cytochrome P450 enzymes through aryl hydrocarbon receptor (AhR). However, little is known about the role of AhR and environmental AhR ligands in diffuse GC as compared to intestinal GC in Western patients. In a cohort of 29, we demonstrated a significant increase in AhR protein and mRNA expression levels in GCs independently of their subtypes and clinical parameters. AhR and RHOA mRNA expression were correlated in diffuse GC. Further, our study aimed to characterize in GC how AhR and the AhR-related genes cytochrome P450 1A1 (CYP1A1) and P450 1B1 (CYP1B1) affect the mRNA expression of a panel of genes involved in cancer development and progression. In diffuse GC, CYP1A1 expression correlated with genes involved in IGF signaling, epithelial-mesenchymal transition (Vimentin), and migration (MMP2). Using the poorly differentiated KATO III epithelial cell line, two well-known AhR pollutant ligands, namely 2-3-7-8 tetrachlorodibenzo-p-dioxin (TCDD) and benzo[a]pyrene (BaP), strongly increased the expression of CYP1A1 and Interleukin1ß (IL1B), and to a lesser extend UGT1, NQO1, and AhR Repressor (AhRR). Moreover, the increased expression of CYP1B1 was seen in diffuse GC, and IHC staining indicated that CYP1B1 is mainly expressed in stromal cells. TCDD treatment increased CYP1B1 expression in KATO III cells, although at lower levels as compared to CYP1A1. In intestinal GC, CYP1B1 expression is inversely correlated with several cancer-related genes such as IDO1, a gene involved in the early steps of tryptophan metabolism that contributes to the endogenous AhR ligand kynurenine expression. Altogether, our data provide evidence for a major role of AhR in GC, as an environmental xenobiotic receptor, through different mechanisms and pathways in diffuse and intestinal GC. Our results support the continued efforts to clarify the identity of exogenous AhR ligands in diffuse GC in order to define new therapeutic strategies.

Polycyclic aromatic hydrocarbon and its adducts in peripheral blood: Gene and environment interaction among Chinese population.

BACKGROUND: Benzo(a)pyrene (B[a]P) is the most widely concerned polycyclic aromatic hydrocarbons (PAHs), which metabolizes benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) in vivo to produce carcinogenic effect on the body. Currently, there is limited research on the role of the variation of metabolic enzymes in this process. METHODS: We carried out a study including 752 participants, measured the concentrations of 16 kinds PAHs in both particle and gaseous phases, urinary PAHs metabolites, leukocyte BPDE-DNA adduct and serum BPDE- Albumin (BPDE-Alb) adduct, and calculated daily intake dose (DID) to assess the cumulative exposure of PAHs. We conducted single nucleotide polymorphism sites (SNPs) of metabolic enzymes, explored the exposure-response relationship between the levels of exposure and BPDE adducts using multiple linear regression models. RESULT: Our results indicated that an interquartile range (IQR) increase in B[a]P, PAHs, BaPeq, 1-hydroxypyrene (1-OHP), 1-hydroxynaphthalene (1-OHNap) and 2-hydroxynaphthalene (2-OHNap) were associated with 26.53 %, 24.24 %, 28.15 %, 39.15 %, 12.85 % and 14.09 % increase in leukocyte BPDE-DNA adduct (all P < 0.05). However, there was no significant correlation between exposure with serum BPDE-Alb adduct (P > 0.05). Besides, we also found the polymorphism of CYP1A1(Gly45Asp), CYP2C9 (Ile359Leu), and UGT1A1(downstream) may affect BPDE adducts level. CONCLUSION: Our results indicated that leukocyte BPDE-DNA adduct could better reflect the exposure to PAHs. Furthermore, the polymorphism of CYP1A1, CYP2C9 and UGT1A1affected the content of BPDE adducts.